To describe the epidemiologic and clinical features associated with invasive amebiasis in Bangladesh, 85 hospitalized diarrheal patients with hematophagous trophozoites of Entamoeba histolytica in their stools were compared to a control group of 84 hospitalized diarrheal patients without amebiasis. Postmortem examinations were carried out in 22 deaths due to amebiasis. For the patients with amebiasis, there was a bimodal age distribution with peaks at 2–3 years and >40 years, whereas the control patients had a unimodal distribution with the peak at 0–1 year. The sex distribution was equal in childhood but young adults were predominantly female and older adults predominantly male. The clinical features significantly associated with amebiasis were prolonged dysentery, prior measles rash, malnutrition, hyponatremia, hypokalemia, and hypoproteinemia (all P < 0.05). The case fatality rate in amebiasis was 29%, which was significantly higher than 11% for the controls (P < 0.05). Postmortem findings included extensive colitis with deep ulcers and complications, including colonic perforation in 2 cases, peritonitis in 4 cases, pneumonia in 9 cases, and septicemia in 5 cases. These results indicate that invasive amebiasis in this population differs from other diarrheal diseases, affecting mainly children > 2 years and adults and causing severe and fatal illness characterized by extensive colitis with diverse systemic consequences.